Importance of Concomitant Viral Infection During Late Acute Liver Allograft Rejection

Çakalǒglu, Yılmaz; Devlin, John; O’Grady, John; Sutherland, Sheena; Portmann, Bernard; Heaton, Nigel; Tan, K. C.; Williams, Roger D.

doi:10.1097/00007890-199501150-00008

Cited by 52 publications

(24 citation statements)

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“…These include less conspicuous bile duct inflammation and venular endothelial inflammation, more prominent interface hepatitis, and more prominent lobular hepatitis with spotty necrosis. [37][38][39][40] Features of chronic hepatitis have also been used in the Hannover scheme for grading chronic rejection. 41 …”

Section: Histological Findingsmentioning

confidence: 99%

“…In addition, as discussed, previous studies have suggested that late cellular rejection may be associated with histological changes different from those typically seen in early acute rejection, more closely resembling those occurring in chronic viral hepatitis or AIH. [37][38][39][40] The majority of patients with a diagnosis of idiopathic posttransplantation chronic hepatitis are clinically asymptomatic. Minor abnormalities of serum biochemistry test results are frequently detected, principally in the form of a mild transaminitis.…”

Section: Idiopathic Posttransplantation Chronic Hepatitismentioning

confidence: 99%

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Recurrent autoimmune hepatitis after liver transplantation: Diagnostic criteria, risk factors, and outcome

Hübscher

2001

Liver Transpl

109

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Approximately 20% to 30% of patients undergoing liver transplantation for autoimmune hepatitis (AIH) develop features of recurrent disease. Diagnostic criteria for recurrent AIH are similar to those used in the nontransplanted liver and include, in varying combinations, biochemical, serological, and histological abnormalities and steroid dependency. However, these criteria are more difficult to apply in the liver allograft because of potential interactions between recurrent AIH and other complications of liver transplantation, particularly rejection, and the uncertain effects of long-term immunosuppression. In the absence of other reliable diagnostic markers, a number of studies have used the histological finding of chronic hepatitis as the main or sole criterion for diagnosing recurrent AIH. However, this also lacks diagnostic specificity because there are many other possible causes of chronic hepatitis in the liver allograft. In addition, approximately 20% to 40% of biopsies performed on patients as part of routine annual review have histological features of chronic hepatitis, for which no definite cause can be identified. Risk factors that have been associated with the development of recurrent AIH include suboptimal immunosuppression, HLA phenotype, disease type and severity in the native liver, and duration of follow up. In many cases in which recurrent AIH seems to be related to underimmunosuppression, biochemical and histological features rapidly resolve once adequate immunosuppression is restored. However, in other cases, recurrent AIH behaves more aggressively, with progression to cirrhosis and graft failure. Areas that require further study include developing uniform criteria for the diagnosis of recurrent AIH, identifying risk factors for severe recurrent disease, and determining optimal levels of immunosuppression that minimize the impact of disease recurrence without exposing patients to the risks of overimmunosuppression. (Liver Transpl 2001;7:285-291.) R ecurrence of autoimmune hepatitis (AIH) after liver transplantation has been reported in several studies. [1][2][3][4][5][6][7][8][9][10][11][12] The reported rate of recurrence ranges from 11% to 83%, with 20% to 30% documented in most studies. Occasional studies have failed to find evidence of recurrent AIH. 13 There is considerable variation in the criteria used to diagnose recurrent AIH and the reported outcome of disease recurrence, and risk factors for recurrent AIH are also poorly understood. The study by Gonzalez-Koch et al, 14 which appears in this edition of Liver Transplantation, provides further evidence that AIH recurs after liver transplantation, but also highlights some problems that exist in diagnosing disease recurrence in the liver allograft. Diagnostic CriteriaThe main problem with establishing a diagnosis of AIH is the lack of a single specific diagnostic marker. In the native liver, AIH is diagnosed on the basis of a constellation of findings, including the presence of positive features that support a diagnosis of AIH and the a...

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Section: Histological Findingsmentioning

confidence: 99%

Section: Idiopathic Posttransplantation Chronic Hepatitismentioning

confidence: 99%

Recurrent autoimmune hepatitis after liver transplantation: Diagnostic criteria, risk factors, and outcome

Hübscher

2001

Liver Transpl

109

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“…In addition, CMV infection has been hypothesized to enhance allograft rejection, although this is controversial. 13 Although it has been difficult to show direct cause and effect between CMV infection and liver allograft rejection, in other types of solid-organ transplantations, decreased graft survival has been observed in patients at high risk for CMV disease (e.g., donor CMV positive, recipient CMV negative [Dϩ/R-]). However, the decrease in immunosuppressive therapy that is often part of the treatment regimen for CMV infection may favor rejection.…”

Section: Clinical Spectrum Of CMV Infection After Oltmentioning

confidence: 99%

Management of cytomegalovirus infection after liver transplantation

Sampathkumar

Payá

2000

Liver Transpl

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“…[5][6][7] In liver transplantation, the importance of concomitant CMV infection during late acute rejections has been reported. 8 An association between CMV and vanishing bile duct syndrome (VBDS) in hepatic allografts has been found, 9 and persistence of CMV DNA in hepatocytes, 10,11 bile ducts, and vascular structures 11 of the liver has been demonstrated in patients with VBDS. We recently showed that persistent CMV infection in liver allografts is associated with chronic rejection.…”

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confidence: 99%

Cytomegalovirus infection is associated with increased inflammation and severe bile duct damage in rat liver allografts

et al. 1998

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It has been suggested that cytomegalovirus (CMV) infection is involved in allograft rejection. In liver transplantation, it has been suggested that CMV is associated with the development of vanishing bile duct syndrome (VBDS), and persistent CMV has been found in liver grafts that develop chronic rejection. In this experimental study, the effect of rat CMV (RCMV) infection on intragraft changes was investigated in a rat model of acute liver allograft rejection. Liver transplantations were performed in a rat strain combination of PVG (RT1 c ) = BN (RT1 n ). No immunosuppression was given. One group of animals was infected with RCMV Maastricht Strain (10 5 plaque-forming units, intraperitoneally), and another group was left uninfected. The grafts were examined histologically after the rats were killed on postoperative days 7 through 9 at the early phase and days 20 through 30 at the late phase of rejection. Immunohistochemical studies were performed to demonstrate the immunological activation markers major histocompatibility complex class II and interleukin 2 receptors, intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), and their ligands. RCMV infection was demonstrated from the grafts by culture and direct antigen detection. In liver allografts undergoing acute rejection, CMV significantly increased portal inflammation and caused more severe bile duct damage than in the uninfected grafts. CMV was also linked to the induction of VCAM-1 in the endothelial cells. The ongoing infection was found to vary over time in the different structures of the liver grafts, including the vascular endothelium and bile ducts. Our results support an association between CMV infection and the immunological mechanisms of rejection, as well as the role of CMV in the development of bile duct damage in liver allografts. (HEPATOLOGY 1998;27;996-1002.)Cytomegalovirus (CMV) infection is a major source of morbidity and mortality in transplant recipients and other immunocompromised patients. The incidence of CMV infection among liver transplant recipients is high, and 40% to 70% of these patients develop a symptomatic CMV disease. 1-4 A variety of clinical manifestations of CMV infection, such as fever, pneumonitis, gastroenteritis, and hepatitis, have been described. The liver is a privileged site for CMV, and the liver graft has been found to be the most commonly affected organ in primary CMV infections. 1 CMV has also been suggested to be linked to organ allograft rejection in both kidney and heart transplantation. [5][6][7] In liver transplantation, the importance of concomitant CMV infection during late acute rejections has been reported. 8 An association between CMV and vanishing bile duct syndrome (VBDS) in hepatic allografts has been found, 9 and persistence of CMV DNA in hepatocytes, 10,11 bile ducts, and vascular structures 11 of the liver has been demonstrated in patients with VBDS. We recently showed that persistent CMV infection in liver allografts is associated with chronic rejection. 11 Va...

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Importance of Concomitant Viral Infection During Late Acute Liver Allograft Rejection

Cited by 52 publications

References 0 publications

Recurrent autoimmune hepatitis after liver transplantation: Diagnostic criteria, risk factors, and outcome

Recurrent autoimmune hepatitis after liver transplantation: Diagnostic criteria, risk factors, and outcome

Management of cytomegalovirus infection after liver transplantation

Cytomegalovirus infection is associated with increased inflammation and severe bile duct damage in rat liver allografts

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